Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Thymidine phosphorylase

Gene

TYMP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.1 Publication
Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.1 Publication

Catalytic activityi

Thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate.

Pathwayi: dTMP biosynthesis via salvage pathway

This protein is involved in step 1 of the subpathway that synthesizes dTMP from thymine.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Thymidine phosphorylase, Thymidine phosphorylase (TYMP), Thymidine phosphorylase (TYMP), Thymidine phosphorylase (deoA)
  2. no protein annotated in this organism
This subpathway is part of the pathway dTMP biosynthesis via salvage pathway, which is itself part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes dTMP from thymine, the pathway dTMP biosynthesis via salvage pathway and in Pyrimidine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei116Substrate1
Binding sitei202Substrate1
Binding sitei217Substrate1
Binding sitei221Substrate1

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • cell differentiation Source: UniProtKB-KW
  • chemotaxis Source: UniProtKB-KW
  • mitochondrial genome maintenance Source: CAFA
  • pyrimidine nucleobase metabolic process Source: InterPro
  • pyrimidine nucleoside catabolic process Source: Reactome
  • pyrimidine nucleoside metabolic process Source: CAFA
  • pyrimidine nucleoside salvage Source: Reactome
  • regulation of gastric motility Source: CAFA
  • regulation of myelination Source: CAFA
  • regulation of transmission of nerve impulse Source: CAFA

Keywordsi

Molecular functionDevelopmental protein, Glycosyltransferase, Growth factor, Transferase
Biological processAngiogenesis, Chemotaxis, Differentiation

Enzyme and pathway databases

BioCyciMetaCyc:HS00442-MONOMER
BRENDAi2.4.2.4 2681
ReactomeiR-HSA-73614 Pyrimidine salvage
R-HSA-73621 Pyrimidine catabolism
SABIO-RKiP19971
UniPathwayiUPA00578; UER00638

Protein family/group databases

MoonDBiP19971 Curated
MoonProtiP19971

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine phosphorylase (EC:2.4.2.4)
Short name:
TP
Alternative name(s):
Gliostatin
Platelet-derived endothelial cell growth factor
Short name:
PD-ECGF
TdRPase
Gene namesi
Name:TYMP
Synonyms:ECGF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000025708.13
HGNCiHGNC:3148 TYMP
MIMi131222 gene
neXtProtiNX_P19971

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Mitochondrial DNA depletion syndrome 1, MNGIE type (MTDPS1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy.
See also OMIM:603041
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01677744R → Q in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs28931613EnsemblClinVar.1
Natural variantiVAR_007643145G → R in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs121913037EnsemblClinVar.1
Natural variantiVAR_007644153G → S in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs121913038EnsemblClinVar.1
Natural variantiVAR_007645222K → R in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs149977726Ensembl.1
Natural variantiVAR_007646289E → A in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs121913036Ensembl.1
Natural variantiVAR_007647397 – 398Missing in MTDPS1. 1 Publication2

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi199Y → A: Abolishes catalytic activity. 1 Publication1
Mutagenesisi199Y → F: Reduced catalytic activity. 1 Publication1
Mutagenesisi199Y → L: Reduced catalytic activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Primary mitochondrial disease, Progressive external ophthalmoplegia

Organism-specific databases

DisGeNETi1890
GeneReviewsiTYMP
MalaCardsiTYMP
MIMi603041 phenotype
OpenTargetsiENSG00000025708
Orphaneti298 Mitochondrial neurogastrointestinal encephalomyopathy
PharmGKBiPA162407502

Chemistry databases

ChEMBLiCHEMBL3106
DrugBankiDB01101 Capecitabine
DB00369 Cidofovir
DB00322 Floxuridine
DB00544 Fluorouracil
DB09343 Tipiracil
DB00432 Trifluridine

Polymorphism and mutation databases

BioMutaiTYMP
DMDMi67477361

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000358741 – 1010
ChainiPRO_000003587511 – 482Thymidine phosphorylaseAdd BLAST472

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP19971
PaxDbiP19971
PeptideAtlasiP19971
PRIDEiP19971
ProteomicsDBi53705

2D gel databases

OGPiP19971

PTM databases

iPTMnetiP19971
PhosphoSitePlusiP19971
SwissPalmiP19971

Expressioni

Gene expression databases

BgeeiENSG00000025708
CleanExiHS_TYMP
ExpressionAtlasiP19971 baseline and differential
GenevisibleiP19971 HS

Organism-specific databases

HPAiCAB002518
HPA000530
HPA001072

Interactioni

Subunit structurei

Homodimer.3 Publications

GO - Molecular functioni

  • growth factor activity Source: UniProtKB-KW
  • protein homodimerization activity Source: CAFA

Protein-protein interaction databases

BioGridi108219, 23 interactors
IntActiP19971, 2 interactors
STRINGi9606.ENSP00000252029

Chemistry databases

BindingDBiP19971

Structurei

Secondary structure

1482
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi36 – 44Combined sources9
Helixi51 – 63Combined sources13
Helixi68 – 81Combined sources14
Helixi85 – 96Combined sources12
Helixi106 – 111Combined sources6
Beta strandi112 – 118Combined sources7
Helixi125 – 134Combined sources10
Turni135 – 137Combined sources3
Beta strandi139 – 143Combined sources5
Helixi154 – 158Combined sources5
Helixi170 – 180Combined sources11
Beta strandi181 – 185Combined sources5
Beta strandi189 – 192Combined sources4
Helixi193 – 204Combined sources12
Helixi211 – 224Combined sources14
Beta strandi228 – 236Combined sources9
Beta strandi240 – 244Combined sources5
Helixi245 – 261Combined sources17
Beta strandi266 – 272Combined sources7
Beta strandi280 – 283Combined sources4
Helixi284 – 294Combined sources11
Helixi300 – 316Combined sources17
Beta strandi319 – 322Combined sources4
Helixi323 – 335Combined sources13
Helixi338 – 349Combined sources12
Helixi354 – 362Combined sources9
Helixi365 – 371Combined sources7
Beta strandi376 – 382Combined sources7
Beta strandi387 – 392Combined sources6
Helixi394 – 405Combined sources12
Beta strandi409 – 412Combined sources4
Beta strandi420 – 423Combined sources4
Beta strandi436 – 446Combined sources11
Helixi449 – 458Combined sources10
Beta strandi459 – 464Combined sources6
Beta strandi475 – 477Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UOUX-ray2.11A12-482[»]
2J0FX-ray2.31A/B/C/D1-482[»]
2WK5X-ray2.99A/B/C/D1-482[»]
2WK6X-ray2.50A/B1-482[»]
ProteinModelPortaliP19971
SMRiP19971
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19971

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati265 – 279R-V-A-A-A-L-X(5,6)-L-G-RAdd BLAST15
Repeati329 – 342R-V-A-A-A-L-X(5,6)-L-G-RAdd BLAST14
Repeati393 – 401R-A-L-X-X-A-L-V-L9
Repeati453 – 461R-A-L-X-X-A-L-V-L9

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IIV8 Eukaryota
COG0213 LUCA
GeneTreeiENSGT00390000009250
HOGENOMiHOG000047313
HOVERGENiHBG000082
InParanoidiP19971
KOiK00758
OMAiVHSIGGV
OrthoDBiEOG091G08UG
PhylomeDBiP19971
TreeFamiTF332198

Family and domain databases

Gene3Di3.40.1030.10, 1 hit
3.90.1170.30, 1 hit
InterProiView protein in InterPro
IPR000312 Glycosyl_Trfase_fam3
IPR017459 Glycosyl_Trfase_fam3_N_dom
IPR036320 Glycosyl_Trfase_fam3_N_dom)sf
IPR035902 Nuc_phospho_transferase
IPR036566 PYNP-like_C_sf
IPR013102 PYNP_C
IPR018090 Pyrmidine_PPas_bac/euk
IPR017872 Pyrmidine_PPase_CS
IPR000053 Thymidine/pyrmidine_PPase
PANTHERiPTHR10515 PTHR10515, 1 hit
PfamiView protein in Pfam
PF02885 Glycos_trans_3N, 1 hit
PF00591 Glycos_transf_3, 1 hit
PF07831 PYNP_C, 1 hit
PIRSFiPIRSF000478 TP_PyNP, 1 hit
SMARTiView protein in SMART
SM00941 PYNP_C, 1 hit
SUPFAMiSSF47648 SSF47648, 1 hit
SSF52418 SSF52418, 1 hit
SSF54680 SSF54680, 1 hit
TIGRFAMsiTIGR02644 Y_phosphoryl, 1 hit
PROSITEiView protein in PROSITE
PS00647 THYMID_PHOSPHORYLASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19971-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAALMTPGTG APPAPGDFSG EGSQGLPDPS PEPKQLPELI RMKRDGGRLS
60 70 80 90 100
EADIRGFVAA VVNGSAQGAQ IGAMLMAIRL RGMDLEETSV LTQALAQSGQ
110 120 130 140 150
QLEWPEAWRQ QLVDKHSTGG VGDKVSLVLA PALAACGCKV PMISGRGLGH
160 170 180 190 200
TGGTLDKLES IPGFNVIQSP EQMQVLLDQA GCCIVGQSEQ LVPADGILYA
210 220 230 240 250
ARDVTATVDS LPLITASILS KKLVEGLSAL VVDVKFGGAA VFPNQEQARE
260 270 280 290 300
LAKTLVGVGA SLGLRVAAAL TAMDKPLGRC VGHALEVEEA LLCMDGAGPP
310 320 330 340 350
DLRDLVTTLG GALLWLSGHA GTQAQGAARV AAALDDGSAL GRFERMLAAQ
360 370 380 390 400
GVDPGLARAL CSGSPAERRQ LLPRAREQEE LLAPADGTVE LVRALPLALV
410 420 430 440 450
LHELGAGRSR AGEPLRLGVG AELLVDVGQR LRRGTPWLRV HRDGPALSGP
460 470 480
QSRALQEALV LSDRAPFAAP SPFAELVLPP QQ
Length:482
Mass (Da):49,955
Last modified:June 7, 2005 - v2
Checksum:i0652FA0B8F3BDE28
GO
Isoform 2 (identifier: P19971-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     386-386: D → DAPLPA

Note: No experimental confirmation available.
Show »
Length:487
Mass (Da):50,405
Checksum:iC2F16246C51DCE00
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195D → E in AAH18160 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01677744R → Q in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs28931613EnsemblClinVar.1
Natural variantiVAR_007643145G → R in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs121913037EnsemblClinVar.1
Natural variantiVAR_007644153G → S in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs121913038EnsemblClinVar.1
Natural variantiVAR_007645222K → R in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs149977726Ensembl.1
Natural variantiVAR_007646289E → A in MTDPS1. 1 PublicationCorresponds to variant dbSNP:rs121913036Ensembl.1
Natural variantiVAR_007647397 – 398Missing in MTDPS1. 1 Publication2
Natural variantiVAR_007648471S → L2 PublicationsCorresponds to variant dbSNP:rs11479EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045556386D → DAPLPA in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63193 mRNA Translation: AAA60043.1
AK225269 mRNA No translation available.
U62317 Genomic DNA Translation: AAB03344.2
BC018160 mRNA Translation: AAH18160.1
BC052211 mRNA Translation: AAH52211.1
CCDSiCCDS14096.1 [P19971-1]
CCDS58811.1 [P19971-2]
PIRiS03904
RefSeqiNP_001107227.1, NM_001113755.2 [P19971-1]
NP_001107228.1, NM_001113756.2 [P19971-1]
NP_001244917.1, NM_001257988.1 [P19971-1]
NP_001244918.1, NM_001257989.1 [P19971-2]
NP_001944.1, NM_001953.4 [P19971-1]
UniGeneiHs.180903
Hs.730607

Genome annotation databases

EnsembliENST00000252029; ENSP00000252029; ENSG00000025708 [P19971-1]
ENST00000395678; ENSP00000379036; ENSG00000025708 [P19971-1]
ENST00000395680; ENSP00000379037; ENSG00000025708 [P19971-1]
ENST00000395681; ENSP00000379038; ENSG00000025708 [P19971-2]
GeneIDi1890
KEGGihsa:1890
UCSCiuc003bmb.7 human [P19971-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTYPH_HUMAN
AccessioniPrimary (citable) accession number: P19971
Secondary accession number(s): A8MW15
, H9KVA0, Q13390, Q8WVB7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: June 7, 2005
Last modified: June 20, 2018
This is version 206 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health